Difamilast
(Synonyms: OPA-15406) 目录号 : GC62589
Difamilast (OPA-15406) 是一种局部的，具有选择性的非甾体磷酸二酯酶 4 (PDE4) 抑制剂，对 B 亚型具有特别有效的抑制作用 (IC50=11.2 nM)。Difamilast 可用于研究轻度至中度特应性皮炎 (AD)。
Cas No.:937782-05-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Difamilast (OPA-15406) is a topical, selective and nonsteroidal phosphodiesterase-4 (PDE4) inhibitor with particularly efficient inhibition of subtype B (IC50=11.2 nM). Difamilast can be used for the research of mild to moderate atopic dermatitis (AD)[1][2][3].
OPA-15406 is highly selective for inhibition of PDE4 subtype B (IC50=11.2 nM), and OPA-15406 also exerts inhibitory effects on PDE2[2].
OPA-1540 improves skin condition in relevant animal models of AD[1].
[1]. Hanifin JM, et, al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016 Aug;75(2):297-305.
[2]. Ahluwalia J, et, al. Phosphodiesterase 4 Inhibitor Therapies for Atopic Dermatitis: Progress and Outlook. Drugs. 2017 Sep;77(13):1389-1397.
[3]. Soeberdt M, et, al. Small molecule drugs for the treatment of pruritus in patients with atopic dermatitis. Eur J Pharmacol. 2020 Aug 15;881:173242.
| Cas No. | 937782-05-3 | SDF | |
| 别名 | OPA-15406 | ||
| 分子式 | C23H24F2N2O5 | 分子量 | 446.44 |
| 溶解度 | DMSO : 100 mg/mL (223.99 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2399 mL | 11.1997 mL | 22.3994 mL |
| 5 mM | 0.448 mL | 2.2399 mL | 4.4799 mL |
| 10 mM | 0.224 mL | 1.12 mL | 2.2399 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial
J Am Acad Dermatol 2022 Mar;86(3):607-614.PMID:34710557DOI:10.1016/j.jaad.2021.10.027.
Background: Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis. Objective: To demonstrate the superiority of Difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis. Methods: In this phase 3, randomized, double-blind trial, patients aged 15-70 years with an investigator global assessment score of 2 or 3 received topical Difamilast ointment 1% (n = 182) or a vehicle (n = 182) twice daily for 4 weeks. Results: The success rate in investigator global assessment score at week 4 (primary endpoint)-the percentage of patients achieving an investigator global assessment score of 0 or 1 with ≥2-grade improvement-was significantly higher with 1% Difamilast than with the vehicle (38.46% vs 12.64%, respectively, P < .0001). The success rates in ≥50%, ≥75%, and ≥90% improvement in overall eczema area and severity index score at week 4 followed the same trend. Difamilast at 1% provided significant mean percent improvement from baseline in overall eczema area and severity index score versus vehicle from week 1 to 4. Treatment-emergent adverse events were mostly mild or moderate and less frequent with Difamilast. Limitations: Study treatment was limited to 4 weeks. Conclusion: Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.
Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial
Br J Dermatol 2022 Jan;186(1):40-49.PMID:34289086DOI:10.1111/bjd.20655.
Background: In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor. Objectives: To demonstrate the superiority of topical Difamilast to vehicle in Japanese paediatric patients with AD. Methods: This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received Difamilast 0·3% (n = 83), Difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks. Results: The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44·6%, 47·1% and 18·1% in the Difamilast 0·3%, Difamilast 1% and vehicle groups, respectively. Both Difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [Difamilast 0·3% (P < 0·001); Difamilast 1% (P < 0·001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of ≥ 50%, ≥ 75% and ≥ 90% in overall score) at week 4 were significantly higher in patients in the Difamilast 0·3% and 1% groups than those in the vehicle group. EASI score in the Difamilast 0·3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the Difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported. Conclusions: Difamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.
What's New in Topicals for Atopic Dermatitis?
Am J Clin Dermatol 2022 Sep;23(5):595-603.PMID:36048410DOI:10.1007/s40257-022-00712-0.
Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and Difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care.
Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study
Dermatol Ther (Heidelb) 2022 Jul;12(7):1589-1601.PMID:35716332DOI:10.1007/s13555-022-00751-9.
Introduction: Phosphodiesterase 4 (PDE4), which regulates inflammatory cytokine production leading to atopic dermatitis (AD), is selectively inhibited by Difamilast. The objective of this phase III, long-term, open-label study was to evaluate the safety and efficacy of topical Difamilast in Japanese adult and pediatric patients with AD. Methods: Adult patients (n = 166) began treatment with Difamilast 1% ointment, and pediatric patients began treatment with Difamilast 0.3% ointment (n = 144) or Difamilast 1% ointment (n = 56). Treatment was continued twice daily for 52 weeks. All patients had an Investigator's Global Assessment (IGA) score of 2 (mild), 3 (moderate), or 4 (severe/very severe), and an AD-affected body surface area (BSA) of ≥ 5% before treatment, with no restriction on the upper limit for the AD-affected BSA. Results: During therapy, 120 adult patients (72.3%) and 178 pediatric patients (89.0%) experienced treatment-emergent adverse events (TEAEs), most of which were mild or moderate in severity. Discontinuation due to TEAEs was reported in 13 adult patients (7.8%) and in 7 pediatric patients (3.5%). Treatment-related adverse events were reported in 14 adult patients (8.4%) and 16 pediatric patients (8.0%), most frequently dermatitis atopic (1.8%) and acne (1.2%) in adult patients and dermatitis atopic and pigmentation disorder (each 2.0%) in pediatric patients. The cumulative success rates in Eczema Area and Severity Index (EASI)-75 in adult and pediatric patients were 55.4% and 73.5%, respectively, at week 52, and the cumulative success rates increased from week 4 to week 52. The cumulative success rates in IGA score showed the same trend as those in EASI -75. Conclusions: This study demonstrates that Difamilast ointments are well tolerated and effective in Japanese adult and pediatric patients with AD when applied twice daily for 52 weeks, and are expected to be used for a long-term treatment for AD. Clinical trial registration: Clinical Trials.gov identifier: NCT03961529.
New Topical Therapies in Development for Atopic Dermatitis
Drugs 2022 Jun;82(8):843-853.PMID:35596877DOI:10.1007/s40265-022-01722-2.
Atopic dermatitis (AD) is a common chronic pruritic inflammatory cutaneous disease. AD is characterized by intense pruritus and enormous clinical heterogeneity. Treatment goals are to improve skin lesions and minimize exacerbations and symptom burden. Currently, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) are still considered the main topical therapies in disease treatment. However, despite being very effective, TCS and TCI are not recommended for continuous long-term use, due to potential safety issues. Although research in AD has focused primarily on systemic drugs, more than 20 new topical compounds are under development to treat the disease. This review aims to provide a synthesized summary of the current knowledge about AD topical treatment, echoing existing gaps and coming research trends. The available data seems promising, with some drugs already approved (ruxolitinib being the most recent), and several are in an advanced stage of development and will soon be available for treatment of mild to moderate disease, namely tapinarof, Difamilast, and roflumilast. However, longer and larger prospective studies are needed to assess the long-term efficacy and safety of these new compounds and evaluate their benefits over current treatments.